Development of a Practical Synthesis of the 8-FDC Fragment of OPC-167832

Vijayagopal Gopalsamuthiram; Dang Ho; Cheryl Peck; Vasudevan Natarajan; Toolika Agrawal; Justina Burns; John Blachert; Daniel Cook; Rodger Stringham; Ryan Nelson; Saeed Ahmad; Frank Gupton; David Snead; Tyler  McQuade; Rajappa Vaidyanathan; Kai Donsbach; Joshua Sieber

doi:10.26434/chemrxiv-2021-37mqc

Organic Chemistry

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Development of a Practical Synthesis of the 8-FDC Fragment of OPC-167832

Working Paper

Vijayagopal Gopalsamuthiram Virginia Commonwealth University ,
Dang Ho Virginia Commonwealth University ,
Cheryl Peck Virginia Commonwealth University ,
Vasudevan Natarajan Virginia Commonwealth University ,
Toolika Agrawal Virginia Commonwealth University ,
Justina Burns Virginia Commonwealth University ,
John Blachert Virginia Commonwealth University ,
Daniel Cook Virginia Commonwealth University ,
Rodger Stringham Virginia Commonwealth University ,
Ryan Nelson Virginia Commonwealth University ,
Saeed Ahmad Virginia Commonwealth University ,
Frank Gupton Virginia Commonwealth University ,
David Snead Virginia Commonwealth University ,
Tyler McQuade Virginia Commonwealth University ,
Rajappa Vaidyanathan Virginia Commonwealth University ,
Kai Donsbach Virginia Commonwealth University ,
Joshua Sieber Virginia Commonwealth University & Medicines for all institute

Abstract

A concise and practical synthesis has been developed to provide the 8-fluoro-5-hydroxy-3,4-diydrocarbostyril (8-FDC) fragment of OPC-167832 in 41 % yield and in > 99 % purity over 4 steps from 3-amino-4-fluorophenol. The key feature of this process is the development of a telescoped one pot synthesis of the quinolone via a chemoselective amidation and easier product isolation without the need for a column chromatography.